New discoveries place lack of energy at the basis of Parkinson’s Disease
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Neuroscientists have demonstrated how a defect in the gene Pink1 results in Parkinson’s disease (PD). By mapping this process at a molecular level, they have provided the ultimate proof that a deficient energy production process in cells can result in Parkinson’s disease. The results of their work have been published in the journal Science.
Mitochondria are cell components that produce the energy required by a cell to function. The action of these mitochondria – and therefore the energy production in cells – is disrupted in Parkinson’s disease. The exact mechanism was unknown. In recent years, scientists have described various gene defects (mutations) in Parkinson’s patients that result in decreased activity of the mitochondria, including a mutation in the Pink1 gene.
Vanessa Moraïs studied the link between Pink1, mitochondria and Parkinson’s disease in fruit-flies and mice with a defective Pink1 gene. These model organisms exhibited symptoms of Parkinson’s disease as a result of this defect. She was able to demonstrate that the defect in Pink1 resulted in the so-called ‘Complex I’ – a protein complex with a crucial role in the energy production of mitochondria – not being phosphorylated adequately, resulting in decreased energy production. When Moraïs and her colleagues ensured correct phosphorylation of Complex I, the Parkinson’s symptoms decreased or disappeared in mice and in patient-derived stem cell lines. The scientists thereby demonstrated that the lack of phosphorylation causes Parkinson’s disease in patients with a defect Pink1 gene.
This study reveals that repairing the phosphorylation of Complex I could be a treatment strategy for Parkinson’s disease. The VIB scientists have already used cells from Parkinson’s patients with a defective Pink1 gene to demonstrate that repairing the phosphorylation results in increased energy production. However, will this cause the symptoms of Parkinson’s disease to decrease or disappear? Only tests on patients can answer this question. According to the scientists, the best strategy would be to start with the sub-group of patients with a defective Pink1 gene. But before starting clinical trials, a lot of aspects still have to be tested.
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Vanessa A. Morais, Dominik Haddad1, Katleen Craessaerts, Pieter-Jan De Bock, Jef Swerts, Sven Vilain, Liesbeth Aerts, Lut Overbergh, Anne Grünewald, Philip Seibler, Christine Klein, Kris Gevaert, Patrik Verstreken, Bart De Strooper. . PINK1 Loss of Function Mutations Affect Mitochondrial Complex I Activity via NdufA10 Ubiquinone Uncoupling. Science, Published Online March 20 2014. doi: 10.1126/science.1249161